This investigation is part of a long-range program directed towards elucidation of the mechanism of hydrocarbon carcinogenesis at the chemical-molecular level. In this phase of this project it is intended to complete studies of the comparative chemical properties of a series of diolepoxide and arene oxide derivatives of polycyclic hydrocarbons of varying biological activity. Reactions of these oxidized metabolites with water, with the model nucleophiles tert-butylthiol and cysteine (models for in vivo reactions with proteins and glutathione), and with nucleic acids are to be investigated in detail. A second major goal will be to test a proposed theory of carcinogenesis through (a) synthesis of the proposed active metabolites (diolepoxides, K-oxides, etc., as appropriate) of a series of carcinogenic hydrocarbons of varying structural types, (b) determination of their effectiveness in alkylating DNA and RNA, and (c) determination of their susceptibility to the action of epoxide hydratase. These compounds will also be made available to interested investigators for metabolism studies and determination of their mutagenic, carcinogenic, and other biological activities. The knowledge gained in all the foregoing studies will be correlated with MO theoretical concepts insofar as possible and incorporated in a more comprehensive theory of metabolic activation and carcinogenesis.